Trefoil factors — new markers of gastrointestinal mucosal barrier

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Trefoil factors (TFFs) are peptides containing a cloverleaf-like structure, which are synthesized in diverse organs including various regions of the human brain (presumably involved in nervous system development and differentiation), thyroid gland, mammary gland, uterus, prostate gland, conjunctiva, respiratory tract, salivary glands, and gall bladder, which peaks in diverse gastrointestinal tract mucosa: TFF-1 — in the stomach, TFF-2 — in the stomach and duodenum, and TFF-3 — in the gut. An increasing body of studies indicate not only about a widely distributed trefoil factors in vivo but also points at their important regulatory functions. In particular, TFFs affect cell adhesion by enhancing epithelial cell migration. Recovery of reversibly damaged epithelial structures called restitution is also facilitated due to TFF-related antiapoptotic effect (anoikis resistance). In contrast, TFF-mediated proangiogenic effects can promote tumor angiogenesis, whereas their immunomodulatory effects include an influence on expression of pro-inflammatory and defense factors (including nitric oxide, cytokines, and defensins). Moreover, TFFs interacting with mucin may increase mucus viscosity, thereby protecting the mucosal layers against ulcerogenic agents. However, bronchial asthma maybe aggravated by elevating mucus viscosity in the respiratory tract due to TFF-2. In addition, TFF expression level is associated with pathogenesis of inflammatory diseases in the gastrointestinal tract. It was shown that modality of changes in TFF level might differ depending on anatomical location and severity of lesions. Changing TFF level plays an important role in oncogenesis. For instance, gastric and colorectal cancer is accompanied by upregulated TFF-1 expression. Importantly, TFF amount is considered as a diagnostic predictor due to being associated with carcinogenesis stage, metastasis as well as sensitivity to chemotherapy in gastrointestinal cancer. In addition, a role potentially played by TFFs in other malignancies including retinoblastoma, breast cancer, and thyroid carcinoma has been extensively examined. Thus, an expanding range of experimental and clinical data evidence that trefoil factors maybe considered as a promising marker of gastrointestinal and oncology diseases.

About the authors

A. V. Shestopalov

Pirogov Russian National Research Medical University; Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology; Center of the Strategic Planning


Alexander V. Shestopalov - PhD, MD (Medicine), Professor, Vice Director of the High School of Molecular and Experimental Medicine at Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology; Head of the Department of Biochemistry and Molecular Biology, Pirogov Russian National Research Medical University; Professor of the Center of the Strategic Planning.

117997, Moscow, Samory Mashela str., 1.

Phone: +7 (495) 287-65-70.

Russian Federation

A. S. Dvornikov

Pirogov Russian National Research Medical University


PhD, MD (Medicine), Dean of the Medical Faculty, Pirogov Russian National Research Medical University.

Russian Federation

O. V. Borisenko

Pirogov Russian National Research Medical University


PhD, MD (Medicine), Associate Professor, Department of Biochemistry and Molecular Biology, Pirogov Russian National Research Medical University.

Russian Federation

A. V. Tutelyan

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology; Central Research Institute of Epidemiology of the Federal Service for Surveillance on Customer Rights Protection and Human Wellbeing

Author for correspondence.

RAS Corresponding Member, PhD, MD (Medicine), Professor, Head of the Department of Molecular Immunology, Infectology and Pharmacotherapy, and the Laboratory of Molecular Visualization, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology; Head of the Laboratory of Infections Associated with the Provision of Medical Care, Central Research Institute of Epidemiology of the Federal Service for Surveillance on Customer Rights Protection and Human Wellbeing.

Russian Federation


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Copyright (c) 2019 Shestopalov A.V., Dvornikov A.S., Borisenko O.V., Tutelyan A.V.

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